The specific aim of the proposal during the period for which support is requested is to study the mechanism of interaction of penicillins and cephalosporins with the multiple penicillin binding components of bacterial cells and with inhibited bacterial enzymes (transpeptidases and D-alanine carboxypeptidases involved in bacterial cell wall synthesis). Detailed studies of the mechanism of interaction of beta-lactam antibiotics with these substances will be undertaken and the relationship of the penicillin binding components, the inhibited enzymes and the killing site of each other will be examined. In addition, studies of mechanism of killing by a number of other antibiotics will be undertaken. In particular, a novel amidino penicillin, bacitracin, and several antibiotics which inhibit the transglycosylation step in bacterial cell wall synthesis will be studied.